A New Biomarker for Beta Cell Death is Revealed

-Craig Idlebrook

A team of researchers has identified a new biomarker that signals the onset of type 1 diabetes, and this substance appears to occur much earlier and more consistently than a previously identified biomarker. Anath Shalev, M.D., the director of the University of Alabama at Birmingham (UAB) Comprehensive Diabetes Center, hopes that this discovery might aid in the diagnosis and treatment of type 1 diabetes in the earliest possible stages of beta cell destruction.

Dr. Shalev’s research, which was published in The American Journal of Physiology-Endocrinology and Metabolism, focused on the body’s tendency to release microRNA-204, or miR-204, when beta cells, which produce insulin, are stressed. MicroRNA are non-coding RNA molecules that help with gene expression. These molecules were once considered “junk”, but scientists now know they play an important part in the regulation of many of the body’s biological functions. Mir-204 helps regulate insulin production, according to Dr. Shalev. 

Anath Shalev, professor

Dr. Anath Shalev, the director of the University of Alabama at Birmingham (UAB) Comprehensive Diabetes Center

“It has a lot of roles in the beta cell in the context of diabetes,” she said in a telephone interview with T1D Exchange. “In addition, it has been shown to be highly enriched in beta cells.”

It is that last characteristic which led Dr. Shalev and her team of researchers at the University of Alabama at Birmingham to wonder whether miR-204 would serve as an indicator of early beta cell destruction. They began to methodically test to see if they could find an increase of the circulation of miR-204 when beta cell destruction occurs – first in rat models, and then in the new onset of type 1 diabetes in children, and then in adults with type 1 diabetes. Elevated levels of miR-204 was found each step of the way. 

They then took it a step further and monitored for miR-204 in those genetically predisposed to type 1 diabetes who also had autoantibodies that indicated they were likely to eventually develop type 1 diabetes; again, elevated miR-204 was found in the bloodstream. In addition, the researchers established an inverse correlation between the levels of miR-204 and beta cell function in the body. 

This same pattern was not found in those with type 2 diabetes, or those with another autoimmune condition, rheumatoid arthritis. In other words, miR-204 appears to be a unique canary in a coalmine when it comes to the health of beta cells and the onset of type 1 diabetes. 

“It’s an indicator that something is wrong with the beta cell and that the beta cell is stressed, and only under stress is it releasing its contents,” Dr. Shalev said. 

Dr. Shalev has long been studying ways to detect and treat type 1 diabetes in the earliest possible stages. In 2018, she and her research team had published a study in Nature Medicine which found that verapamil, a common blood pressure medication, could help promote the body’s natural insulin production in adults with recent onset type 1 diabetes. 

This is not the first biomarker discovered to detect the onset of type 1 diabetes; another biomarker is autoantibody positivity. However, Dr. Shalev said that miR-204 can detect beta cell destruction earlier and with a less expensive clinical test. 

“We believe we have a marker,” she said. “It’s not perfect by any stretch, but we have a marker that is sensitive enough to detect early and relatively subtle beta cell death.”

In the future, she envisions the possibility of combining known biomarkers to create a signature of beta cell health that may help diagnose the onset of type 1 diabetes much earlier and more accurately than previously possible. It may even help clinicians decide when to begin treatment to prolong beta cell function.  

“The way I envision it, if one combines this biomarker with the antibody positivity, you can get a much better handle on who of those at-risk patients will have a diagnosis of diabetes more imminently, and those would be the ones we want to treat,” she said.

To read a press release about this research, click here

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Editor’s note: The above photo of cells was not taken as part of this study. 

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